New Mesothelioma Biomarker Emerges as Prime Target for Chemotherapy Drugs
April 4, 2011
A 2010 study sponsored by the National Institute of Health and the Mesothelioma Applied Research Foundation identified a new biomarker that may make chemotherapeutic treatments for mesothelioma more effective.
Researchers found melanoma cell adhesion molecule (MCAM) to be a more precise biomarker than mesothelin, which is currently the most common focus of malignant mesothelioma biomarker studies. This study considered MCAM’s potential as a biomarker for the disease as well as a primary receptor for chemotherapy drugs.
MCAM may be regarded as more promising than mesothelin because while it has been identified in each subtype of the cancer, it is not found in healthy mesothelial cells. In a collection of tissues that included specimens of sarcomatoid, epithelioid and mixed type cancers, MCAM was identified in more than 80 percent of the total samples. In this study, MCAM was expressed in 28 of 31 epithelioid tissue samples, eight of 10 sarcomatoid samples and 14 of 14 mixed type samples.
Mesothelin, on the other hand, is notably absent in sarcomatoid mesothelioma cells. One previous study found mesothelin in 44 of 44 epithelioid mesotheliomas but none of eight sarcomatoid cancers. Mesothelin is also found in healthy mesothelial cells, yet MCAM is only present in malignant cells, making it a more accurate receptor for anti-cancer drugs. MCAM can also indicate angiogenesis, which occurs when healthy cells become cancerous, by its presence in tumor-associated blood vessels.
After identifying MCAM as an accurate biomarker for the cancer, the second phase of the study explored its potential as a therapeutic target. The prevalence of MCAM in each type of malignant mesothelioma made it a more appealing subject for potential targeted chemotherapy treatments than mesothelin, which would be limited to treating tumors made of epithelioid cells.
Five assorted tumor fragments were exposed to a prominent anti-MCAM substance, scFv, within laboratory testing dishes. The substance bound only with the tumors, indicating that the anti-MCAM scFv can specifically target the cells. An in vivo test confirmed the targeting specificity of the anti-MCAM small molecule drugs. The antibody was also shown to increase cytotoxicity, or selective cellular destruction, in tumors that were targeted by the drugs.
The discovery of MCAM as a highly responsive biomarker in mesothelioma tissues may offer new options for clinical treatment of this therapy-resistant cancer.